A successful kidney transplant is the best treatment for established renal failure, yet around 300 patients per annum are denied transplants because they have antibodies, most notably directed against donor HLA or ABO in their blood, which have the potential to cause acute and chronic rejection of the transplant. Such antibodies are present in 25% (roughly 1750 of the 7000 on the kidney transplant waiting list) of the patients listed for a deceased donor transplant. Programmes to remove antibody and transplant patients across HLA antibody barriers have been developed, but are limited by a high rate of acute rejection. This thesis explores the factors which may impact upon the pathogenicity of HLA-specific antibodies and also aims to enhance the understanding of the techniques used in the laboratory to define these antibodies. A range of studies were carried out examining factors such as the IgG subclass composition of the anti-HLA response. Assay variations were designed to enable a higher definition of antibody specificity to be achieved, and for the first time in the literature the direct quantification of HLA-specific antibodies in patient sera was performed. In addition, proof of principle design and testing was carried out on a novel prototype therapeutic device for the selective depletion of HLA-specific antibodies directly from patient plasma and sera. The antibodies isolated from this approach were also used in studies to examine the factors which determine serum cytotoxicity.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:582488 |
| Date | January 2013 |
| Creators | Lowe, David Philip |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/58070/ |
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